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High-density lipoprotein inhibits human M1 macrophage polarization through redistribution of caveolin-1.

Authors :
Lee, Man K S
Moore, Xiao ‐ Lei
Fu, Yi
Al ‐ Sharea, Annas
Dragoljevic, Dragana
Fernandez ‐ Rojo, Manuel A
Parton, Robert
Sviridov, Dmitri
Murphy, Andrew J
Chin ‐ Dusting, Jaye P F
Moore, Xiao-Lei
Al-Sharea, Annas
Fernandez-Rojo, Manuel A
Chin-Dusting, Jaye P F
Source :
British Journal of Pharmacology; Feb2016, Vol. 173 Issue 4, p741-751, 11p
Publication Year :
2016

Abstract

<bold>Background and Purpose: </bold>Monocyte-derived macrophages are critical in the development of atherosclerosis and can adopt a wide range of functional phenotypes depending on their surrounding milieu. High-density lipoproteins (HDLs) have many cardio-protective properties including potent anti-inflammatory effects. We investigated the effects of HDL on human macrophage phenotype and the mechanisms by which these occur.<bold>Experimental Approach: </bold>Human blood monocytes were differentiated into macrophages in the presence or absence of HDL and were then induced to either an inflammatory macrophage (M1) or anti-inflammatory macrophage (M2) phenotype using LPS and IFN-γ or IL-4, respectively.<bold>Key Results: </bold>HDL inhibited the induction of macrophages to an M1-phenotype, as evidenced by a decrease in the expression of M1-specific cell surface markers CD192 and CD64, as well as M1-associated inflammatory genes TNF-α, IL-6 and MCP-1 (CCL2). HDL also inhibited M1 function by reducing the production of ROS. In contrast, HDL had no effect on macrophage induction to the M2-phenotype. Similarly, methyl-β-cyclodextrin, a non-specific cholesterol acceptor also suppressed the induction of M1 suggesting that cholesterol efflux is important in this process. Furthermore, HDL decreased membrane caveolin-1 in M1 macrophages. We confirmed that caveolin-1 is required for HDL to inhibit M1 induction as bone marrow-derived macrophages from caveolin-1 knockout mice continued to polarize into M1-phenotype despite the presence of HDL. Moreover, HDL decreased ERK1/2 and STAT3 phosphorylation in M1 macrophages.<bold>Conclusions and Implications: </bold>We concluded that HDL reduces the induction of macrophages to the inflammatory M1-phenotype via redistribution of caveolin-1, preventing the activation of ERK1/2 and STAT3. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00071188
Volume :
173
Issue :
4
Database :
Complementary Index
Journal :
British Journal of Pharmacology
Publication Type :
Academic Journal
Accession number :
112756432
Full Text :
https://doi.org/10.1111/bph.13319